Medicine and Health Sciences Commons^™

An Exploration Of Patients' Trust In Physicians In Training, Denise Bonds, Kristie Foley, Elizabeth Dugan, Mark Hall, Pam Extrom

Elizabeth Dugan

Several characteristics associated with patient trust are identified. To determine the level of trust patients from disadvantaged circumstances have in their primary care resident physician, and to determine patient and physician characteristics that predict trust, we administered a survey to randomly selected primary care patients of an academic medical center staffed by internal medicine residents after a visit to their primary care provider. Participants were adults. The group was racially diverse (50% non-white), English-speaking, and from lower socioeconomic groups. The 10-page survey consisted of 7 sections (Physician Trust Scale, Patient Demographics, Patient Health and Well-Being, Patient-Physician Relationship Characteristics, Global Doctor …

The Impact On Patient Trust Of Legalising Physician Aid In Dying, Mark Hall, Felicia Trachtenberg, Elizabeth Dugan

Elizabeth Dugan

OBJECTIVE: Little empirical evidence exists to support either side of the ongoing debate over whether legalising physician aid in dying would undermine patient trust. DESIGN: A random national sample of 1117 US adults were asked about their level of agreement with a statement that they would trust their doctor less if "euthanasia were legal [and] doctors were allowed to help patients die". RESULTS: There was disagreement by 58% of the participants, and agreement by only 20% that legalising euthanasia would cause them to trust their personal physician less. The remainder were neutral. These attitudes were the same in men and …

The Effects Of Implementation Of The Agency For Health Care Policy And Research Urinary Incontinence Guidelines In Primary Care Practices, Deirdre Bland, Elizabeth Dugan, Stuart Cohen, John Preisser, Cralen Davis, Paul Mcgann, Patricia Suggs, Katherine Pearce

Elizabeth Dugan

OBJECTIVES: To determine whether a multifaceted intervention based on the Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guidelines for Urinary Incontinence would increase primary care physician screening for and management of urinary incontinence (UI). DESIGN: Group randomized trial, conducted from 1996 to 1997. SETTING: Internal medicine and family medicine community practices. PARTICIPANTS: Forty-one primary care practices, including 57 physicians and their staff and 1,145 patients aged 60 and older. INTERVENTION: Twenty of the 41 primary care practices in North Carolina were randomized to a composite intervention that included a 3-hour continuing medical education accredited course, training in …

The Impact Of A Video Intervention On The Use Of Low Vision Assistive Devices, Robert Goldstein, Elizabeth Dugan, Felicia Trachtenberg, Eli Peli

Elizabeth Dugan

PURPOSE: An image-enhanced educational and motivational video was developed for patients with low vision and their caretakers. Impact on knowledge, self-efficacy, and attitudes was assessed. METHODS: The video incorporated cognitive restructuring to change emotional response; a "virtual home"; a veridical simulation of vision with age-related macular degeneration and contrast enhancement of the video. Subjects (median age 77.5) were randomized into control (n=79) and intervention (n=75) groups. Telephone interviews were at baseline, 2 weeks and 3 months. Main outcome measures were: knowledge (eight questions), self-efficacy score (seven questions), adaptive behaviors (10 questions), willingness to use devices, and emotional response (4-point scales). …

Baseline Experience With Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (Whims), Stephen Rapp, Mark Espeland, Patricia Hogan, Beverly Jones, Elizabeth Dugan

Elizabeth Dugan

The Modified Mini Mental State Exam (3MS) is widely used for screening global cognitive functioning, however little is known about its performance in clinical trials. We report the distribution of 3MS scores among women enrolled in the Women's Health Initiative Memory Study (WHIMS) and describe differences in these scores associated with age, education, and ethnicity. The 3MS exams were administered to 7,480 women aged 65-80 who had volunteered for and were eligible for a clinical trial on postmenopausal hormone therapy. General linear models were used to describe demographic differences among scores. Factor analysis was used to characterize the correlational structure …

Prevalence Of Sexual Abuse Among Women Seeking Gynecologic Care In Germany, Ursula Peschers, Janice Du Mont, Katharina Jundt, Mona Pfurtner, Elizabeth Dugan, Gunther Kindermann

Elizabeth Dugan

OBJECTIVE: To estimate the prevalence of sexual abuse among patients seen for gynecologic care in Germany. METHODS: A short anonymous questionnaire was distributed to 1157 women attending a gynecologic outpatient clinic at a large urban teaching hospital. Data collected using the questionnaire included patient characteristics, sexual abuse history, and screening practices. Women who reported that they had been abused were asked if they had ever discussed the issue with their gynecologist. RESULTS: A total of 1075 questionnaires were returned, for a response rate of 92.9%. Almost half (n = 479 [44.6%]) of the women surveyed reported that they had been …

Racial Disparity In Pregnancy-Related Mortality Following A Live Birth Outcome, Margaret Harper, Mark Espeland, Elizabeth Dugan, Robert Meyer, Kathy Lane, Sharon Williams

Elizabeth Dugan

PURPOSE: African-American women have a 2- to 4-fold increased risk of pregnancy-related death compared with Caucasian women. We conducted this study to determine if differences in a combination of socioeconomic and medical risk factors may explain this racial disparity in pregnancy-related death. METHODS: Pregnancy-related deaths of African-American (N=60) and Caucasian (N=47) women were identified from review of pregnancy-associated deaths (N=400) ascertained through cause of death on death certificates, electronic linkage of birth and death files, and review of the hospital discharge database for the State of North Carolina, during the period between 1992 and 1998. Controls (N=3404) were randomly selected …

How Patients' Trust Relates To Their Involvement In Medical Care, Felicia Trachtenberg, Elizabeth Dugan, Mark Hall

Elizabeth Dugan

OBJECTIVES: To examine the connection between patients' trust and their attitudes toward seeking care, participating in medical decision making, and adhering to treatment recommendations. METHODS: Data were collected from a national telephone survey of English-speaking adults (N=553) in 1999. Eligibility requirements were some type of public or private health care coverage and having seen a physician or other health professional at least twice in the past 2 years. Five questions on preferred role in medical care were asked. Trust in physicians and satisfaction with care were separately measured using validated scales. RESULTS: The most significant predictor of patients' preferred role …

Addressing The Controversy Of Rate-Versus-Rhythm Control In Atrial Fibrillation, Tahmeed Contractor, Vadim Levin, Ravi Desai, Francis E Marchlinski

Vadim A Levin MD

Atrial fibrillation is the most common sustained cardiac arrhythmia and significantly increases patient risk of stroke, cardiomyopathy, and mortality. Rate versus rhythm control as the "best" treatment strategy remains an issue of considerable, ongoing debate. A multitude of clinical trials have compared the 2 strategies and have not shown any benefit of one approach over the other. However, the trials were conducted in specific subgroups of patients and demonstrated low success rates with antiarrhythmic drug (AAD) therapy and a high incidence of adverse AAD effects. Sub-analyses of the trials have confirmed that successful rhythm control with sinus rhythm restoration is …

Addressing The Controversy Of Rate-Versus-Rhythm Control In Atrial Fibrillation, Tahmeed Contractor, Vadim Levin, Ravi Desai, Francis E Marchlinski

Ravi V Desai MD

Atrial fibrillation is the most common sustained cardiac arrhythmia and significantly increases patient risk of stroke, cardiomyopathy, and mortality. Rate versus rhythm control as the "best" treatment strategy remains an issue of considerable, ongoing debate. A multitude of clinical trials have compared the 2 strategies and have not shown any benefit of one approach over the other. However, the trials were conducted in specific subgroups of patients and demonstrated low success rates with antiarrhythmic drug (AAD) therapy and a high incidence of adverse AAD effects. Sub-analyses of the trials have confirmed that successful rhythm control with sinus rhythm restoration is …

Adverse Drug Events After Hospital Discharge In Older Adults: Types, Severity, And Involvement Of Beers Criteria Medications, Abir Kanaan, Jennifer Donovan, Nerissa Duchin, Terry Field, Jennifer Tjia, Sarah Cutrona, Shawn Gagne, Lawrence Garber, Peggy Preusse, Leslie Harrold, Jerry Gurwitz

Jennifer Tjia

OBJECTIVES: To characterize adverse drug events (ADEs) occurring within the high-risk 45-day period after hospitalization in older adults.

DESIGN: Clinical pharmacists reviewed the ambulatory records of 1,000 consecutive discharges.

SETTING: A large multispecialty group practice closely aligned with a Massachusetts-based health plan.

PARTICIPANTS: Hospitalized individuals aged 65 and older discharged home.

MEASUREMENTS: Possible drug-related incidents occurring during the 45-day period after hospitalization were identified and presented to a pair of physician-reviewers who classified incidents as to whether an ADE was present, whether the event was preventable, and the severity of the event. Medications implicated in ADEs were further characterized according …

Long Term Recall Of Memory Cd8 T Cells In Mice To First And Third Generation Smallpox Vaccines, Sharone Green, Francis Ennis, Anuja Mathew

Sharone Green

Since long-term immunity is a critical component of any effective vaccine, we compared over a 15-month period, the strength, durability and specificity of immunity of an attenuated smallpox vaccine Modified Vaccinia Ankara (MVA) to the New York City Board of Health (NYCBH) vaccine. The frequencies of CD8(+) T cells to an immunodominant CD8 T cell epitope B8R(20-27) remained remarkably stable in mice given either MVA or NYCBH. Both groups were also protected from a lethal intranasal challenge with Western Reserve strain of vaccinia virus (VACV-WR). Cytokine responses to virus-specific peptides were detectable with significant boosting upon challenge. Expression of most …

Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Sharone Green

Plasma leakage in dengue hemorrhagic fever (DHF) is associated with elevated plasma levels of cytokines. To define further the contribution of immune activation to DHF and the source of cytokines, we analyzed the production of cytokines in peripheral blood mononuclear cells (PBMC) obtained from children with dengue, using RT-PCR and immunostaining. Tumor necrosis factor-alpha (TNF-alpha) and TNF-beta expression was detected in all samples by PCR and in < 50% of samples by immunostaining. Interferon-gamma (IFN-gamma) expression was detected in < 50% of samples by either method. Interleukin-2 (IL-2) and IL-4 expression was detected in a few samples by immunostaining but was not …

The Safety And Tolerability Of An Hiv-1 Dna Prime-Protein Boost Vaccine (Dp6-001) In Healthy Adult Volunteers, Jeffrey Kennedy, Mary Co, Sharone Green, Karen Longtine, Jaclyn Longtine, Melissa O'Neill, Janice Adams, Alan Rothman, Qiao Yu, Renita Johnson-Leva, Ranajit Pal, Shixia Wang, Shan Lu, Phillip Markham

Sharone Green

This report describes the safety observations following administration of a polyvalent DNA prime-protein boost HIV-1 vaccine formulated with adjuvant QS21. Local injection site reactions were the most common (65% of subjects), and included type IV delayed-type hypersensitivity (DTH) reactions at prior DNA inoculation sites in 12 of 28 (43%) subjects following protein vaccination. Systemic reactions revealed two cases of vasculitis temporally related to inoculation with recombinant Env protein+QS21 adjuvant. Questions remain regarding the cause of the vasculitis, but the unique DTH observation may have contributed to the high level of immune responses previously reported for this vaccine.

Invited Commentary On: Orthotopic Heart Transplantation In Patients With Metabolic Risk Factors, Nicholas Cavarocchi, Paul Mather

Nicholas C Cavarocchi MDJ

This is invited commentary to the following article: Kilic, A., Conte, J. V., Shah, A. S., & Yuh, D. D. (2012). Orthotopic heart transplantation in patients with metabolic risk factors. Annals of Thoracic Surgery, 93(3), 718-724.

Development And Characterization Of A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis In Mice, Thomas Greenough, Gregory Babcock, Anjeanette Roberts, Hector Hernandez, William Thomas, Jennifer Coccia, Robert Graziano, Mohan Srinivasan, Israel Lowy, Robert Finberg, Kanta Subbarao, Leatrice Vogel, Mohan Somasundaran, Katherine Luzuriaga, John Sullivan, Donna Ambrosino

William D Thomas Jr

BACKGROUND: Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARS-CoV) could provide protection for exposed individuals. METHODS: Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection. RESULTS: Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed …

Treatment With Monoclonal Antibodies Against Clostridium Difficile Toxins, Israel Lowy, Deborah Molrine, Brett Leav, Barbara Blair, Roger Baxter, Dale Gerding, Geoffrey Nichol, William Thomas, Mark Leney, Susan Sloan, Catherine Hay, Donna Ambrosino

William D Thomas Jr

BACKGROUND: New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection.

METHODS: We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo.

RESULTS: …

Therapy With A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody Reduces Disease Severity And Viral Burden In Golden Syrian Hamsters, Anjeanette Roberts, William Thomas, Jeannette Guarner, Elaine Lamirande, Gregory Babcock, Thomas Greenough, Leatrice Vogel, Norman Hayes, John Sullivan, Sherif Zaki, Kanta Subbarao, Donna Ambrosino

William D Thomas Jr

BACKGROUND: Immunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and for the treatment of cancers and autoimmune diseases. MAb 201 is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific MAb that prevents establishment of viral replication in vitro and prevents viral replication in vivo when administered prophylactically. The efficacy of MAb 201 in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model that supports SARS-CoV replication to high levels and displays severe pathological changes associated with infection, including pneumonitis and pulmonary consolidation. METHODS: Golden Syrian hamsters that …

Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias Schnell, Laurence Eisenlohr, Scott Waldman

Adam E Snook

Cancer mucosa antigens are emerging as a new category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors. These antigens leverage the established immunologic partitioning of systemic and mucosal compartments, limiting tolerance opposing systemic antitumor efficacy. An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization. In the context of cancer mucosa antigens, immune effectors to self-antigens risk amplifying mucosal inflammatory disease promoting carcinogenesis. Here, we examined the relationship between immunotherapy for systemic colon cancer metastases targeting the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) and its effect on inflammatory …

Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.

METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with …

Managed Care, Hospice Use, Site Of Death, And Medical Expenditures In The Last Year Of Life, Ezekiel Emanuel, Arlene Ash, Wei Yu, Gail Gazelle, Norman Levinsky, Olga Saynina, Mark Mcclellan, Mark Moskowitz

wei yu

BACKGROUND: We examined deaths of Medicare beneficiaries in Massachusetts and California to evaluate the effect of managed care on the use of hospice and site of death and to determine how hospice affects the expenditures for the last year of life.

METHODS: Medicare data for beneficiaries in Massachusetts (n = 37 933) and California (n = 27 685) who died in 1996 were merged with each state's death certificate files to determine site and cause of death. Expenditure data were Health Care Financing Administration payments and were divided into 30-day periods from the date of death back 12 months.

RESULTS: …

Antipsychotic Use Among Nursing Home Residents, Becky Briesacher, Jennifer Tjia, Terry Field, Daniel Peterson, Jerry Gurwitz

Jennifer Tjia

The prescribing of antipsychotic medications persists at high levels in US nursing homes (NHs) despite extensive data demonstrating marginal clinical benefits and serious adverse effects, including death.1- 2 However, imprecise and outdated data have limited the understanding of the current state of antipsychotic medication prescribing in NHs.3 We analyzed recent and detailed NH prescription data to address: (1) What is the current level of antipsychotic use? (2) Does antipsychotic use in NHs display geographic variation? and (3) Which antipsychotics are most commonly prescribed?

Prognostic Factors For Male Breast Cancer: Similarity To Female Counterparts, Edward Yu, Larry Stitt, Olga Vujovic, Kurian Joseph, Avi Assouline, Joseph Au, Jawaid Younus, Francisco Perera, Patricia Tai

Edward Yu

Abstract. Aim: To assess whether prognostic factors in male (MBC) and female (FBC) breast cancer have similar impact on survival. Patients and Methods: Charts for men and women diagnosed with breast cancer referred to the London Regional Cancer Program (LRCP) were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with/without hormone and radiation therapy (RT), overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female …

Phase Ii Clinical Trial Of Ixabepilone In Patients With Recurrent Or Persistent Platinum- And Taxane-Resistant Ovarian Or Primary Peritoneal Cancer: A Gynecologic Oncology Group Study, Koen De Geest, John Blessing, Robert Morris, S. Diane Yamada, Bradley Monk, Susan Zweizig, Daniela Matei, Carolyn Muller, William Richards

Koen De Geest

PURPOSE Ixabepilone (BMS-247550) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer. The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma. PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma, defined as progression during or within 6 months of one prior course of treatment with each agent, received intravenous ixabepilone 20 mg/m(2) administered over 1 hour on days 1, 8, and 15 of a 28-day cycle. RESULTS Of 51 patients entered, …

A Phase Ii Study Of Docetaxel In Paclitaxel-Resistant Ovarian And Peritoneal Carcinoma: A Gynecologic Oncology Group Study, Peter Rose, John Blessing, Harrison Ball, James Hoffman, David Warshal, Koen Degeest, David Moore

Koen De Geest

OBJECTIVES: Docetaxel is an inhibitor of microtubule depolymerization and has demonstrated activity in paclitaxel-resistant breast cancer and gynecologic cancer. The Gynecologic Oncology Group (GOG) conducted a study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma to determine its activity, and nature and degree of toxicity, in this cohort of patients.

METHODS: Patients with platinum- and paclitaxel-resistant ovarian or peritoneal carcinoma, defined as progression while on or within 6 months of therapy, were eligible if they had measurable disease and had not received more than one chemotherapy regimen. Docetaxel at a dose of 100 mg/m(2) was administered iv over 1 h …

Perceptions Of Evidence-Based Programs Among Community-Based Organizations Tackling Health Disparities: A Qualitative Study, Shoba Ramanadhan, Josephine Crisostomo, Jaclyn Alexander-Molloy, Ediss Gandelman, Milagro Grullon, Vilma Lora, Chrasandra Reeves, Clara Savage, Kasisomayajula Viswanatha, Chyke Doubeni

Chyke A. Doubeni

Dissemination of prevention-focused evidence-based programs (EBPs) from research to community settings may improve population health and reduce health disparities, but such flow has been limited. Academic-community partnerships using community-based participatory research (CBPR) principles may support increased dissemination of EBPs to community-based organizations (CBOs). This qualitative study examined the EBP-related perceptions and needs of CBOs targeting underserved populations. As part of PLANET MassCONECT, a CBPR study, we conducted six key informant interviews with community leaders and four focus groups with CBO staff members in Boston, Worcester and Lawrence, Massachusetts, in 2008. Working definitions of EBPs among CBO staff members varied greatly …

Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader

Dr Robert Brown

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated …

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …